The overall objective of this proposal is to investigate neural substrate systems in the cat of two electrophysiological markers of aging, the surface recorded P300 endogenous response and the middle latency P1 response. In the human, abnormalities in the P300 and P1 occur in normal aging and the P300 changes are exacerbated in Alzheimer's disease. Other changes observed in the aging brain and in Alzheimer's disease include descreased cholinergic activity and cell loss within the basal forebrain system. Model systems of the P300 and P1 in the cat suggest that cholinergic components of the basal forebrain and reticular activating systems may be critically involved in the generation of these potentials. One specific aim of this research will be to test the hypothesis that the cholinergic basal forebrain system is critically involved in P300 generation. The following experiments will be carried out in conjunction with surface recordings of P300 in the cat: a. Effects of lesions in the septo-hppocampal and the nucleus basalis-association cortex components of the basal forebrain system (1) upon the P300 and (2) upon choline acetyltransferase (ChAT)-immunoreactive cells or upon acetylcholinesterase (AChE) strained fibers; b. Depth mapping of P300 local field potentials in the septo-hippocampal and nucleus basalis-association cortex components, combined with fluorescent trace injection and ChAT immunohistochemistry, to test for cholinergic projections between P300 inversion sites. c. Effects of a cholinergic agonist and antagonist upon the P300. The second aim will be to test the hypothesis that the cholinergic component of the ascending reticular activating system (RAS) is critically involved in P1 generation. The following experiments will be carried out in conjunction with surface recordings of P1 (or Wave A) in the cat: a. Effects on lesions in pedunculopontine tegmental (PPT) and intra lamina thalamic components of RAS (1) upon P1 and (2) upon ChAT labelled cells or upon AChE stained fibers; b. Depth mapping of P1 local field potentials in PPT and intralaminar thalamus, combined with fluorescent tracer injection and ChAT immunohistrochemistry, to test for cholinergic projections between P1 inversion sites. c. Effects of a cholinergic agonist an antagonist upon P1.